Increased infectivity of HIV type 1 particles bound to cell surface and solid-phase ICAM-1 and VCAM-1 through acquired adhesion molecules LFA-I and VLA-4

HIV-1 incorporates a variety of host membrane proteins during budding. We h ave previously shown that adhesion molecules are acquired by the virus in t heir activated or functional states. Our studies and those of others indica te that adhesion molecules can have profound effects on virus infectivity a nd its resistance to neutralization by antiviral antibodies. In this study we have examined the effect on infectivity of immobilization or margination of HIV-1 through acquired integrins LFA-1 and VLA-4 onto nonsusceptible ce lls and solid-phase adhesion ligands (ICAM-1 and VCAM-1, respectively). LFA -1- and VLA-4-mediated HIV-1 binding was supported by ICAM-1 and VCAM-1 imm unoglobulin Fc chimeras, respectively, Integrin-mediated HIV-1 binding was also supported by 293 cells transfected with ICAM-1. In both cases the spec ificity of binding was confirmed with the appropriate blocking monoclonal a ntibodies or soluble adhesion ligands. We used a sensitive single-cycle inf ection assay based on a cell line expressing an LTR-luciferase cDNA constru ct to compare the infectivity of bound virus with that of free virus. Our r esults show that the binding of HIV-1 to nonsusceptible cells or immobilize d adhesion ligands through acquired integrins can increase its infectivity by as much as two orders of magnitude. These results have implications for in vivo dissemination and transmission of HIV-1 and may also explain the hi gh level of virus replication seen in solid lymphoid organs.